Thiazolidinediones

Thiazolidinediones
April 2008
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Thiazolidinediones

If you have Type 2 Diabetes, your body still makes enough insulin, but it is unable to use the insulin effectively (termed--"insulin resistance"). Insulin is required to move sugar from the bloodstream into cells of the body for use as energy. The thiazolidinediones ("thigh-a-zo-li-deen-die-owns") are used with diet and exercise to treat people with Type 2 Diabetes, alone or in combination with other drugs. They lower blood sugar by helping the cells of the body use insulin more efficiently to remove excess sugar from the blood.

Drugs in this Class
Pioglitazone Tablets ( Actos Tablets, Pioglitazone Hydrochloride Tablets )
Rosiglitazone ( Avandia )

Summarizing the Evidence

* Few head-to-head trials have directly compared Actos to Avandia. One small study performed at Mayo Clinic showed Actos and Avandia to be similar in their ability to lower HbA1C levels ("hemoglobin- A1C") a blood test that measures diabetic control). Other non-comparative studies and clinical observations have shown that both drugs are similarly effective at improving blood sugar control in patients with Type 2 diabetes.

* Based on limited data, Actos appears to have a more favorable effect on cholesterol levels than Avandia. A few studies have demonstrated that Actos can actually lower total cholesterol levels while Avandia can actually increase cholesterol levels. However, well-controlled, large-scale, head-to-head trials are still needed to fully ascertain this difference.

* Actos and Avandia currently require periodic liver function monitoring (this is done through blood tests as determined by your doctor). However, the risk of liver toxicity is lower than that noted with Rezulin (troglitazone), another drug in this class that was removed from the market.

* Additionally, both Actos and Avandia can cause fluid retention and should be used cautiously in patients with more severe forms of heart failure.

* More recently, Avandia has been linked to an increased risk of heart attack, and the maker of Avandia has agreed to add new warnings to the drug's labeling. Despite the revised warning label, the FDA is not seeking to have the drug withdrawn from the market, because the evidence for the increased heart attack risk is not conclusive. It is not clear whether Actos carries the same heart attack risk as Avandia.

* Both drugs can be used alone or in combination with a sulfonylurea (such as glimepiride, glipizide or glyburide), metformin, or insulin. Actos has been combined with metformin into a combination product called Actoplus Met. Avandia has been combined with metformin into a combination product called Avandamet. Avandia has also been combined with glimepiride into a combination product called Avandaryl. These combination products may be useful for individuals who have difficulty remembering to take multiple medications. However, none of these combination products are available generically.

* Since the thiazolidinediones are similarly effective, the choice of which to use generally depends on your doctor's preference and/or your prescription benefits formulary.

Dosing and Administration

* Both Actos and Avandia are taken once daily with or without food. However, Avandia has demonstrated better effectiveness when given twice daily as compared with once daily.

Generic Availability

* Neither Actos nor Avandia are currently available in generic formulations.

Drug Interactions

Some interactions between medications can be more severe than others. The best way for you to avoid harmful interactions is to tell your doctor and/or pharmacist what medications you are currently taking, including any over-the-counter products, vitamins, and herbals. For specific information on how the drugs interact and the severity of the interaction, please use our Drug Interactions Checker.

Side Effects

To view specific side effect information, please use our Side Effect Checker.

References

1. Avandia [package insert]. Research Triangle Park, NC: GlaxoSmithKline; December 2005.

2. Actos [package insert]. Lincolnshire, IL: Takeda Pharmaceuticals America, Inc. and Indianapolis, IN: Eli Lilly and Company; August 2004.

3. Delea TE, Edelsberg JS, Hagiwara M, et al. Use of thiazolidinediones and risk of heart failure in people with Type 2 diabetes. A retrospective cohort study. Diabetes Care 2003; 26:2983-2989.

4. Nesto RW, Bell D, Bonow RO, et al. Thiazolidinedione use, fluid retention, and congestive heart failure. A consensus statement from the American Heart Association. Diabetes Care 2004; 27:256-263.

5. Khan MA, St. Peter JV, Xue JL. A prospective, randomized comparison of the metabolic effects of pioglitazone or rosiglitazone in patients with type 2 diabetes who were previously treated with troglitazone. Diabetes Care. 2002;25:708-11.

6. Boyle PJ, King AB, Olansky L, et al. Effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus: a retrospective review of randomly selected medical records. Clin Ther. 2002;24(3):378-396.

7. LaCivita KA, Villarreal G. Differences in lipid profiles of patients given rosiglitazone followed by pioglitazone. Curr Med Res Opin. 2002;18(6):363-370.

8. King AB. A comparison in a clinical setting of the efficacy and side effects of three thiazolidinediones. Diabetes Care 2000;23:557.

9. Al-Salman J, Arjomand H, Kemp DG, Mittal M. Hepatocellular injury in a patient receiving rosiglitazone. A case report. Ann Intern Med. 2000;132(2):121-124.

10. Forman LM, Simmons DA, Diamond RH. Hepatic failure in a patient taking rosiglitazone. Ann Intern Med. 2000;132(2):118-121.

11. Gouda HE, Klan A, Schwartz J, Cohen RI. Liver failure in a patient treated with long-term rosiglitazone therapy. Am J Med. 2001;111(7):584-585.

12. Maeda K. Hepatocellular injury in a patient receiving pioglitazone [letter]. Ann Intern Med. 2001;135:306.

13. May LD, Lefkowitch JH, Kram MT, Rubin DE. Mixed hepatocellular-cholestatic liver injury after pioglitazone therapy. Ann Intern Med. 2002;136:449-52.

14. Pinto AG, Cummings OW, Chalasani N. Severe but reversible cholestatic liver injury after pioglitazone therapy. Ann Intern Med. 2002;137(10):857.

15. Mathisen A, Geerlof J, Houser V. The effect of pioglitazone on glucose control and lipid profile in patients with type 2 diabetes [abstract]. Diabetes. 1999;48(1):0441.

16. Data on file. Lincolnshire, IL: Takeda America Research and Development Center, Inc.; July 1999.

17. Aronoff S, Rosenblatt S, Braithwaite S, Egan JW, Mathisen AL, Schneider RL. Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes. Diabetes Care. 2000;23(11):1605-1611.

18. Rubin C, Egan J, Schneider R. Combination therapy with pioglitazone and insulin in patients with type 2 diabetes [abstract]. Diabetes. 1999;48(1):0474.

19. Goldberg RB, Kendall DM, Deeg MA et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with Type 2 diabetes and dyslipidemia. Diabetes Care 2005;28:1547-1554.

20. Einhorn D, Rendell M, Rosenzweig J, et al. Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-controlled study. Clin Ther. 2000;22(12):1395-1409.

21. Nissen SE and Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. New England Journal of Medicine. 2007 Jun 14;356(24):2457-71.
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